The carotid body chemoreceptors are responsible for the increase in ventilation in response to hypoxia. This response develops with time after birth and, from various studies on ventilation alone, it has been concluded that the carotid chemoreceptor responses to O2 and CO2 develop postnatally. Exactly what the responses of the carotid chemoreceptor afferents are in the newborn and how these responses develop is essentially unknown. It is the overall objective of the research proposed here to provide a detailed characterization of the carotid body chemoreceptor afferent responses in the kitten as it develops postnatally. The specific aims of this project are: 1) to quantitatively measure the carotid chemoreceptor responses to O2 and CO2 and their interaction, if any, in the kitten; 2) to measure the responsiveness of the kitten chemoreceptors to pharmacological agents which influence chemoreceptor activity in the adult; 3) to determine the time course and the nature of the development of the carotid chemoreceptor O2 and CO2 responses with time after birth; 4) to investigate the mechanism of development of the carotid body chemoreceptor O2 and CO2 responses in order to explain the differences between the chemoreceptor responses of the newborn and the adult. Carotid chemoreceptor afferent activity will be recorded from a strand of the cut carotid sinus nerve in anesthetized, paralyzed, and artificially ventilated kittens in 4 different age groups (1-3 days old, 7-9 days old, 4 weeks old, and 4 months old). In all age groups, PaO2 and PaCO2 response curves and the responsiveness of the chemoreceptors to pharmacological agents will be measured. In doing so, the changes in the chemoreceptor responses with postnatal age will be assessed. After the basic responses have been investigated, the possible mechanisms underlying the development of the responses will be explored. The dopamine receptor blocker, domperidone, will be used to investigate the possibility that the chemoreceptor responses in the kitten are low because they are suppressed by a high endogenous dopamine release and that this suppression decreases with postnatal age. Acetazolamide, a carbonic anhydrase inhibitor, will be used to investigate if carbonic anhydrase development is involved in the development of the carotid body responses. This project will therefore provide basic information about the carotid chemoreceptor O2 and CO2 responses in the newborn kitten and their development with postnatal age and begin to investigate the possible mechanisms underlying this development.